JP2010509987A - Myocardial ischemia treatment device - Google Patents

Abstract

  A method and apparatus for treating myocardial ischemia is described in which the stress experienced by a myocardial region identified as being prone to ischemia is altered with early excitatory pacing. In the reduced load mode, pacing is applied near the vulnerable area to reduce stress and metabolic demand of the vulnerable area. In the load mode, pacing is applied to an area far from the vulnerable area to produce a conditioning effect.

Description

  The present invention relates to cardiac rhythm management devices, such as pacemakers and other implantable devices.

[Description of related applications]
This application is a priority application of US patent application Ser. No. 11 / 561,049 filed on Nov. 17, 2006, and this US patent application is incorporated by reference. As part of

  Myocardial ischemia refers to a condition in which blood supply to a region of the myocardium (ie, the myocardium) is greatly impaired, and adequate oxygen for oxidative metabolism is not supplied to this region. Ischemia is associated with reduced metabolic byproduct removal, unlike hypoxia, where perfusion is not reduced. The heart is an aerobic (aerobic) organ that generates most of the energy from the oxidation of substances by oxygen sent by the blood. The heart can produce a slight oxygen deficiency and is therefore very sensitive to disruption of the blood supply. Myocardial ischemia occurs when there is an imbalance between oxygen supply and oxygen demand as a result of increased myocardial oxygen demand (demand), decreased myocardial oxygen supply, or both. Due to myocardial ischemia, many patients experience chest pain or discomfort called angina. Angina pectoris serves as a useful warning of inadequate myocardial perfusion, which can lead to more severe conditions such as heart attacks or cardiac arrhythmias.

  Coronary artery disease (CAD) occurs when the coronary artery that supplies blood to the myocardium becomes hardened and stenotic due to the deposition of atherosclerotic plaque. Atherosclerotic plaques are inflammatory reaction sites within the walls of arteries and are composed of a core containing inflammatory cells surrounded by lipids and connective tissue capsules. Myocardial infarction (MI) or heart attack is when an atherosclerotic plaque in the coronary artery ruptures, thereby exposing blood to a lipid core that has a high degree of thrombogenic plaque formation (thrombosis) in the artery. To happen. Complete or near-complete occlusion to coronary blood flow can damage a fairly large area of heart tissue and cause sudden death, usually due to abnormal heart rhythms that prevent effective pumping (cardiac pump function). is there.

  The presence of coronary artery occlusion due to CAD may result in temporary imbalances in oxygen supply and demand due to increased myocardial oxygen requirements caused, for example, by physical exertion or emotional distress. Such demand ischemia may cause a condition called exertional angina or chronic stable angina. In other situations, imbalance may occur acutely due to a sudden decrease in blood flow, sometimes referred to as supply ischemia. Acute blood flow disruption may occur following coronary vasospasm, causing a condition called unstable angina. As described above, acute blood flow disruption may also occur due to coronary thrombosis causing MI. Myocardial ischemia often occurs due to both increased oxygen demand and decreased supply.

FIG. 2 illustrates a physical configuration of an exemplary pacing device. FIG. 3 illustrates components of an example device. FIG. 2 is a block diagram of electronic circuitry of an exemplary device. FIG. 6 is a diagram illustrating an example algorithm that switches between a normal mode and a vulnerable area reduction and load mode. FIG. 6 illustrates an exemplary algorithm for dynamically changing an AV delay interval when delivering early excitement pacing.

  Myocardial ischemia is usually treated with agents that act to either increase myocardial perfusion or decrease myocardial oxygen demand. Surgical revascularization (revascularization) procedures may also be performed to increase blood supply. For the purpose of treating myocardial ischemia employing electrical stimulation that can be delivered, for example, by an implantable cardiac device to cause vasodilation and / or vasoconstriction of one or more coronary arteries. Another intervention is disclosed.

[Mechanical effects of pacing therapy]
When the ventricle is stimulated to contract by a pacing pulse delivered through an electrode placed at a particular pacing site, the excitation spreads from the pacing site by conduction through the myocardium. This is the normal physiological situation where the spread of excitement from the AV node to the ventricle utilizes the heart's intrinsic conduction system composed of Purkinje fibers, which allows rapid and synchronized excitation of the entire ventricular myocardium. Is different. On the other hand, the excitement caused by the pacing pulse causes a relatively asynchronous (asynchronous) contraction because the rate at which the excitement is transmitted from the pacing site to the rest of the myocardium is slow. Thus, regions of the myocardium that are located farther from the pacing site become more excited later than regions near the pacing site, as compared to the intrinsic contraction. As described above, this results in redistribution of myocardial wall stress.

  The degree of tension applied to the muscle fiber before the muscle fiber contracts is called preload, and the degree of tension applied to the muscle fiber when the muscle fiber is contracted is called afterload. By increasing the preload, the muscle fibers are stretched and their maximum tension and shortening speed are increased during contraction. With respect to the heart, the preload of a particular myocardial region is the diastole myocardial wall stress due to end-diastolic pressure and the force exerted by adjacent regions. Myocardial region afterload is myocardial wall stress during systole due to the pressure load on which the heart must pump. As the myocardial region contracts slowly relative to other regions, the contraction of these other regions stretches the later contracting region and increases its preload, thus increasing the contractile force produced by this region. On the contrary, the preload received by the myocardial region that contracts quickly with respect to other regions is reduced, and the generated contact force is small. The pressure in the ventricle quickly rises from the diastolic value to the systolic value when blood is pumped into the aorta and pulmonary arteries, so that the part of the ventricle that contracts quickly during systole later contracts It contracts against a lower afterload than the ventricular part. Delivery of pacing pulses to the ventricular region causes the region to contract faster than other parts of the ventricle. Thus, the paced area undergoes both a pre-load reduction and a post-load reduction, thereby reducing the mechanical stress experienced by the paced area relative to other areas during systolic contraction. On the other hand, regions that are far away from the paced region are subject to increased mechanical stress.

[Early excitement pacing to treat myocardial ischemia]
All but a small fraction of the total amount of oxygen consumed by the myocardium is for the purpose of active muscle contraction during systole, and the oxygen demand of a specific myocardial region increases the systolic wall stress. It increases as Thus, by causing a particular myocardial region to contract faster than other regions, its metabolic demand is reduced and the degree of ischemia that may be present is reduced. One or more sites in or around the fragile region are pre-excited with respect to the remainder of the ventricle to cause premature contraction and reduced stress on the myocardial region that is prone to ischemia. Electrical stimulation pacing pulses may be delivered to such sites in a mechanical deloading manner. Pacing the ventricle at a single site near the fragile region or thus pacing at multiple ventricular sites near the fragile region to perform early excitement pacing therapy to deload the fragile region good. In the latter case, the pacing pulses may be delivered to the multisites simultaneously or in a prescribed pulse output sequence. Single-site or multi-site pacing may be performed according to a bradycardia pacing algorithm such as, for example, suppressed demand mode or trigger mode.

  As described above, the implantable cardiac device may include one or more pacing electrodes that are placed at an early excitation pacing site proximate to the fragile region. In this case, the device may be programmed to operate in the fragile zone deload mode with the early excitement pacing pulses in the fragile zone according to the programmed pacing mode. Early excitatory pacing reduces ischemia that may be present by relieving stress on the vulnerable area and reducing metabolic demand in that area. In this case, the device may be programmed to operate continuously or intermittently in the vulnerable area reduction mode. In the latter case, the device may return to normal mode when the vulnerable area deload mode ends, which may have any form of pacing (e.g., bradycardia or cardiac resynchronization pacing) Or it may not have pacing at all. In this case, the device may have one or more of the following starting conditions (inlet conditions), eg 1) activation of a patient-operated switch that the patient can operate when angina occurs, 2) Receiving a telemetry command to initiate the mode and / or 3) debilitating the fragile region from the normal mode according to the device detecting the presence of myocardial ischemia according to the sensed variable correlated with the presence of myocardial ischemia You can switch to mode. Examples of sensed variables that reflect myocardial ischemia include, in patients with sensed cardiac electrical activity and / or demand ischemia, variables related to effort levels such as heart rate, minute ventilation and activity. Features derived from the level. Further, the fragile area deloading mode may be terminated when one or more designated events or conditions called termination conditions (exit conditions) are detected. Such termination conditions include, for example, non-detection of the presence of myocardial ischemia, elapsed time, activation of a patient-operated switch and / or receipt of a telemetry command that terminates the mode.

  In order to cause premature contractions to other areas paced by early excitatory pacing, these other areas should not be excited by intrinsic excitement transmitted from the AV node. If the fragile region deloading mode delivers early excitatory pacing in arterial tracking or AV sequential pacing mode, the AV delay interval extends beyond the site where the depolarization is pre-excited compared to the patient's unique AV interval; It should be chosen to be short enough to excite the rest of the myocardium without interference from inherent excitement. The shorter the AV delay interval is relative to the patient's inherent AV interval, the more pre-excited the site that is paced. In one embodiment, the device provides an AV delay interval in fragile region deloading mode, eg, according to a sensing variable correlated to the presence of myocardial ischemia as described above to provide for early excitement that reduces stress. It is configured to dynamically shorten. For example, the AV delay interval can be shortened according to the measured heart rate or effort level. This shortening of the AV delay interval also compensates for the physiological shortening of the patient's intrinsic AV interval that occurs as the heart rate increases.

  Another use of early excitation pacing in the treatment of myocardial ischemia is to intentionally stress the vulnerable area by pacing at sites that are located far away from the vulnerable area. As described above, such pacing increases mechanical stress on the fragile region by delaying the fragile region's contraction during the systole relative to other regions. By intermittently applying stress to the vulnerable area, the level of myocardial ischemia in the body area of patients with demand ischemia is lowered, thereby promoting angiogenesis and possibly preconditioning the vulnerable area. To ensure that the vulnerable area is well tolerated by the effects of the next ischemic event. Therefore, the apparatus may be configured to intermittently switch from the normal mode or the vulnerable area deloading mode to the vulnerable area load mode that sends early excitement pacing to a site located far from the vulnerable area. Such early excitement pacing may be delivered at AV delay intervals shortened or dynamically shortened as described above to facilitate early excitement. The intermittent switching to the vulnerable area load mode may be controlled according to one or more start conditions and one or more end conditions, where such start and end conditions are the elapsed time. , Heart rate, activity level measured by accelerometer, and minute ventilation. Because the fragile zone loading mode is designed to cause low-level myocardial ischemia, the fragile zone loading mode is false because the patient is at rest and either because of increased metabolic demand or decreased blood supply. It is desirable to use it only when no blood appears. For example, the start condition to enter the vulnerable area load mode may be that the measured heart rate and / or the effort level is below a specified threshold, and the end condition to end the vulnerable area load mode is the measurement It may be that the heart rate and / or effort level given is above some specified threshold. The additional start and end conditions may be an elapsed time based on a schedule that is defined so that the vulnerable zone load mode is only adopted at certain points in the day and / or is limited in duration. .

[Example implantable device]
FIG. 1 illustrates an implantable cardiac device 100 that delivers early excitatory therapy, and possibly other forms of pacing therapy, to a vulnerable area. Implantable pace sink devices are typically routed intravenously into the heart so that the leads are placed in the heart chamber and connect to electrodes used for sensing and / or pacing. In the condition, it is placed subcutaneously or submuscularly in the patient's chest. The electrode may be positioned on the epicardium by various means. A programmable electronic controller causes pacing pulses to be output in response to elapsed time and / or sensed electrical activity (i.e., intrinsic heartbeat not as a result of pacing pulses). The device senses intrinsic cardiac electrical activity by one or more sensing channels, each sensing channel containing one or more of the electrodes. One or more pacing pulses with energy higher than a certain threshold are passed through one or more pacing channels to excite myocardial tissue in the absence of intrinsic heartbeat Each of the pacing channels contains one or more of the electrodes. FIG. 1 shows an exemplary device with two leads 200, 300, each lead being a multipolar (ie, multi-electrode) lead with electrodes 201, 202 and electrodes 301-304, respectively. is there. Electrodes 201, 202 are placed in the right ventricle to excite or sense the right ventricle and / or septal region, and electrodes 301-304 are in the coronary sinus to excite or sense the left ventricle. Be placed. When the fragile region VR is located in the apex region of the left ventricle, the fragile region deloading module sends out early excitation pacing in the form of bipolar pacing via the electrodes 303 and 304 to deload the fragile region. Such early excitation pacing may be delivered as pacing the left ventricle only or biventricular pacing with an offset such that the left ventricle is paced before the right ventricle, for example. In contrast, in the fragile zone load mode, early excitation pacing is delivered via electrodes 201, 202 in the right ventricle only pacing mode or via electrodes 301, 302 in the right ventricle only or biventricular pacing mode. It is better to excite the myocardial region located far away from the region. Other embodiments can use any number of electrodes in the form of monopolar and / or multipolar leads to excite different myocardial sites. As described below, once the device and lead are implanted, the pacing and / or sensing channel of the device is a selected one of a number of electrodes for selectively pacing or sensing a particular myocardial site. It is good to be equipped with.

  FIG. 2 illustrates the components of the implantable device 100 in detail and illustrates an exemplary monitoring / programming system. The implantable device 100 has a hermetically sealed housing 130 that is placed subcutaneously or submuscularly in a patient's chest. The housing 130 may be made of a conductive metal, such as titanium, which can serve as an electrode that delivers electrical stimulation or senses in a monopolar configuration. A header 140, which may be made of an insulating material, is attached to the housing 130 for receiving the leads 200, 300, which in this case are electrically connected to the pulse generation circuit and / or the sensing circuit. Is good. Housed within the housing 130 is an electronic circuit 132 that provides functionality to the devices described herein, which can be programmed to control the operation of the power supply, sensing circuit, pulse generation circuit, and device. There may be a telemetry transceiver that can communicate with the electronic controller and external programmer or remote monitor device 190. An external programmer communicates wirelessly with the device 100 and allows the clinician to receive data and change the controller's programming. The remote monitoring device can also communicate with the device 100 via telemetry and can further interface to a network 195 (eg, an internet connection) that communicates with the patient management server 196, which allows the clinical practitioner to You can be in a remote location and receive information or issue commands from a remote monitoring device. When a specific condition is detected (eg when a measurement parameter exceeds or falls below a specified limit), the device sends a warning message to the remote monitoring device and to the patient management server for clinical engagement. It should be programmed to alert the person.

  A block diagram of circuit 132 is shown in FIG. A battery 22 supplies power to the circuit. The controller 10 controls the overall operation of the device according to programmed instructions and / or circuit configurations. The controller may be embodied as a microprocessor-based controller, such a controller having a microprocessor and memory for storing data and programs, and a dedicated hardware component such as an ASIC (eg, a finite state machine). Or may be embodied as a combination thereof. The controller further includes a timing circuit, such as an external clock, that embodies a timer used to measure elapsed time and schedule events. As used herein, the term “controller programming” refers to a specific configuration of hardware components that perform code or specific functions that are executed by a microprocessor. The sensing circuit 30 and the pulse generation circuit 20 are interfaced to the controller, and the controller 30 interprets the sensing signal and controls the delivery of the stimulation pulse. The sensing circuit 30 receives an atrial and / or ventricular electrogram signal from the sensing electrode, which sense circuit, an analog-to-digital converter that digitizes the sensing signal input from the sensing amplifier, and the gain and threshold of the sensing amplifier. It has a writable register to adjust The pulse generation circuit 20 delivers stimulation pulses to electrodes arranged for vasoactive stimulation or pacing, the pulse generation circuit comprising capacitive discharge pulse generators, registers controlling the pulse generators and stimulation parameters such as pulses Has a register to adjust energy (eg, pulse amplitude and width). This device allows adjustment of the pacing pulse energy to ensure capture of myocardial tissue by the pacing pulse (ie, the onset of the propagating action potential). Myocardial sites near the ischemic region may be less excitable than normal sites and may require increased pacing energy to achieve capture. The pacing pulse energy for the preexcited ischemic region can be adjusted by programming the device via a telemetry interface according to an electrophysiological test to determine the appropriate pacing pulse energy or, eg, 29 June 2006 Can be automatically adjusted by the automatic capture function described in US patent application Ser. No. 11 / 427,517. The pulse generation circuit may further include a shock pulse generator for delivering a defibrillation / cardiac defibrillation shock via the shock electrode when detecting an anti-tachyarrhythmia. A telemetry transceiver 80 is interfaced to the controller such that the controller can communicate with an external programmer and / or a remote monitor unit. A magnetically actuated or contact actuated switch 24 is also shown interfaced to the controller so that the patient can signal certain conditions or events to the implantable device.

The pacing channel is composed of a pulse generator connected to the electrode, and the sensing channel is composed of a sense amplifier connected to the electrode. Electrodes 40 ₁ to 40 _N are shown, where N is an integer. The electrodes may be located on the same or different leads, and such electrodes are electrically connected to the MOS switch matrix 70. The switch matrix 70 is controlled by a controller, which is used to switch selected electrodes to the sense amplifier input or pulse generator output to configure the sensing or pacing channel, respectively. The device may comprise any number of pulse generators, amplifiers and electrodes that can be arbitrarily combined to form sensing or pacing channels and vectors. The switch matrix 70 allows a selected one of the available implanted electrodes to be incorporated into the sensing and / or pacing channel in either a monopolar configuration or a bipolar configuration. Bipolar sensing or pacing configuration means the sensing of a potential or the output of a pacing pulse between two closely spaced electrodes, in this case two electrodes (e.g. a ring of bipolar leads and a tip electrode or multipolar The two selected electrodes of the lead) are usually located on the same lead. A unipolar sensing or pacing configuration is where the sensed potential or pacing pulse output by the electrode is referenced to the conductive device housing or another remotely located electrode.

  The apparatus shown in FIG. 3 is configured with multiple sensing and / or pacing channels, which may be either the atrium or ventricular sensing / pacing channel or vasoactive stimulation channel, depending on the location of the electrodes. It is good to be done. Thus, the device can deliver single-site or multi-site ventricular pre-excitation pacing for stress reduction / increase as well as conventional pacing purposes. With the switch matrix, certain myocardial sites can be pre-excited for stress reduction or augmentation purposes by selecting appropriately placed electrodes to be incorporated into the pacing channel used to deliver pre-excitation pacing. The configuration of the pacing and sensing channels can be performed automatically by the device by an external programmer communicating via the telemetry interface and upon switching to or from the various operating modes.

  Early excitement pacing can be delivered as single-site pacing, biventricular pacing that prematurely excites one of the ventricles relative to the other as defined by the programmed biventricular offset interval, or as multi-site ventricular pacing Can be sent out. When delivering early excitement pacing to many sites, the sites may be paced simultaneously or according to a specific pulse output sequence that specifies the order and timing at which the sites should be paced during a single heartbeat. If the electrogram signal in the atrial or ventricular sensing channel exceeds a certain threshold, the controller detects the atrial or ventricular sense, respectively, and the pacing algorithm is used to synchronize or suppress pacing. May be used. The controller can operate the device in a number of programmed modes that define how much pacing pulses are output in response to the sensed event and the end of the time interval. Early excitation pacing of one or more ventricular sites located near or far from the fragile region may be delivered in conjunction with a bradycardia pacing mode, which imposes a certain minimum heart rate. By pacing algorithm, such early excitation pacing may or may not include pacing pulses delivered to the atrium or ventricle for other purposes (eg, treatment of bradycardia). The suppressed demand brady pacing mode utilizes a refill contract interval that controls pacing according to the sensed intrinsic activity. In the suppressed demand ventricular pacing mode, the ventricle is paced during the cardiac cycle only after the end of a defined refill contract interval, and no intrinsic heartbeat due to the heart chamber is sensed during such defined refill interval. For example, a ventricular replacement contraction interval can be defined between ventricular events to resume at each ventricular sense or pace, referred to as a low rate interval (LRI). The reciprocal replenishment interval is the minimum rate at which the ventricle can beat, depending on the pacemaker, and may be referred to as the low rate limit (LRL). Also, the pace can be delivered in a rate-adaptive pacing mode that is changed by, for example, the accelerometer 26 or the minute ventilation sensor 25 according to the effort level at which the refill contraction interval is measured. In the atrial tracking and AV sequential pacing modes, another ventricular replacement contraction interval is defined between the atrial and ventricular events and is referred to as the atrioventricular interval or AV interval. The atrioventricular interval is synchronized by the atrial sense or pace and stopped by the ventricular sense or pace. If a ventricular sense does not occur before the end of the atrioventricular interval, the ventricular pace is delivered at the end of the atrioventricular interval. By delivering early excitement pacing at a short AV interval (eg, 30-80% of the intrinsic interval) relative to the patient's intrinsic AV interval, depolarization extends beyond the early excitement site, and there is no interference from the intrinsic excitement and the myocardium Early excitement is facilitated by allowing the remainder of the layer to be excited.

  The implantable device may further have the automatic capture, automatic threshold and reconstruction functions described in US patent application Ser. No. 11 / 427,517, filed Jun. 29, 2006. Is particularly useful for delivering early excitement pacing to vulnerable areas. This is because the excitability characteristics of the fragile region may change over time. Thus, the device may be configured to automatically adjust the early excitement pacing pulse energy and / or the early excitement pacing site to maintain acquisition by the early excitement pacing pulse. In order to determine whether the pacing pulse has achieved capture, a capture verification test is performed, where the capture verification test detects an elicited response to the early excitation pacing pulse. The evoked response sensing channel selects the appropriate electrode, which may be the same electrode used to deliver the pacing pulse, or another electrode located near the pacing site. Therefore, it is configured using a switch matrix. Confirmation of capture by the pacing panel compares the evoked response electrogram signal following the pace to a predetermined threshold, which can be performed by a controller or other dedicated circuitry. If the evoked response electrogram signal exceeds the threshold, it is assumed that capture has occurred. To determine the minimum pacing energy upon detection of a capture failure, an automatic threshold procedure may be performed by a device that determines a minimum pacing threshold. In this case, the pacing pulse energy is adjusted accordingly to match the minimum pacing threshold defined with an appropriate safety margin. Automatic pacing electrode reconfiguration that entails a pacing site change until one is found that can be captured upon detection that no capture has taken place and the automatic capture function reduces the pacing pulse energy for a particular pacing site. This may be done if the available pacing pulse amplitude and width supported by the device cannot be adjusted to a level suitable for performing capture again. The pacing electrode reconstruction algorithm may also be performed periodically or upon command. Such reconstruction may be performed in advance of the available pacing electrodes that list the electrodes in a preferred order of use as determined by clinical trials so that the reconstruction algorithm selects the most suitable pacing location for early excitation pacing. It should be carried out according to a programmed instruction list.

[Detection of myocardial ischemia]
If the blood supply to a region of the myocardium is compromised, the supply of oxygen and other nutrients may be insufficient for the cardiomyocyte metabolic process to maintain these normal polarization states. Thus, the ischemic region of the heart becomes abnormally depolarized during at least a portion of the cardiac cycle, causing current to flow between the ischemic region of the heart and the normally polarized region, which is damaged. Called current. The injury current may be caused by an infarct that is permanently depolarized or by an ischemic region that remains abnormally depolarized during all or part of the cardiac cycle. Ischemia and infarction can affect the magnitude of depolarization and the rate at which depolarization moves through the myocardium. All of these effects result in abnormal changes in the potential caused by cardiac excitation reflected by either surface electrocardiogram or intracardiac electrogram. Thus, the device may be configured to detect the presence of myocardial ischemia from one or more sensed variables associated with cardiac electrical activity.

  The device may be configured to detect cardiac ischemia from morphological analysis of electrocardiograms collected during intrinsic or paced heartbeats, the latter being associated with evoked responses. Sometimes called. As described above, an abnormal change in the potential measured by the intracardiac electrogram occurs as a result of the damaging current. If abnormal ventricular depolarization continues throughout the cardiac cycle, a zero potential is measured only when the rest of the ventricular myocardium is depolarized, which is between the end of the QRS complex of the electrogram and the T-wave. It corresponds to time and is called ST (Estee) wave. After ventricular depolarization, clearly indicated by the T wave of the electrogram, the measured potential is affected by the injury current and is shifted positively or negatively relative to the ST wave depending on the location of the ischemic or infarcted area Will come to be. Traditionally, however, it is the ST wave that is considered shifted when an abnormal damage current is detected by an electrogram or electrocardiogram. Damage currents caused by ischemic regions that do not last throughout the cardiac cycle may only shift part of the ST wave, resulting in an abnormal gradient of the ST wave. Damage currents can also occur when ischemia causes prolonged depolarization in the ventricular region, resulting in an abnormal T wave when the direction of the repolarization wave changes. In order for the device to detect changes in the electrogram representing ischemia, the recorded electrogram is analyzed and compared to a reference electrogram, which is either the entire recorded electrogram or a specific electrogram representing the electrogram It should be one of the reference values. Since certain patients may always show damaging currents in the electrogram (eg, due to CAD or as a result of electrode implantation), the controller compares the recorded electrogram with the reference electrogram. It may be programmed to sense ischemia by looking for an increase in the damage current in the reference electrogram may or may not indicate the damage current. One approach to look for an increase in the damage current in the recorded electrogram is to compare the ST wave amplitude and / or slope to the reference electrogram amplitude and slope. For example, various digital signal processing techniques can be used for analysis using the first and second derivatives to identify the start and end of the ST wave. In another method for searching for the damage current, for example, the recording electrogram and the reference electrogram are cross-correlated to determine their similarity. In this case, the electrogram may be implicitly recorded by passing the electrogram signal through a matched filter that cross-correlates the signal to a reference electrogram. Further, the ST wave may be integrated, and as a result, the integrated value is compared with the reference value to determine whether there is an increase in damage current.

  As noted above, other sensed variables may also indicate the presence of myocardial ischemia, particularly in patients with exertion angina. Thus, the device is based on sensed variables such as heart rate, activity level, local heart motion, local tissue impedance and ventilation per minute in addition to or instead of the above-described techniques based on cardiac electrical activity. It should be programmed to detect the presence of myocardial ischemia with a reasonable probability. To add specificity to the detection scheme, for example, the device senses the damage current and the patient's heart rate and / or effort level (measured by activity level or minute ventilation) above a specified threshold. It should be programmed to detect myocardial ischemia only when it is high.

[Example of embodiment]
In order to apply early excitatory therapy as described above to a myocardial region that is prone to ischemia, this region must be anatomically located so that one or more pacing electrodes can be placed nearby. Don't be. The ischemic field can be located by many means, such as ultrasound imaging, PET scan, thallium scan and MRI perfusion scan. A stress test may be performed to induce myocardial ischemia in patients with demand ischemia. A myocardial region identified as an ischemic region or an ischemic region is considered a fragile region that can be mechanically loaded or de-loaded with early excitation pacing therapy. After implantation and proper placement of the electrodes, the device can then include one or more of the pre-excited pacing located near and / or far from the vulnerable area identified according to a particular pacing mode. It may be programmed with appropriate sensing and pacing channels to deliver to the site.

  An exemplary implantable pacing device includes one or more leads with first and second electrodes that can be placed at different pacing sites. In the exemplary electrode arrangement, the first electrode is placed near a ventricular region that is prone to ischemia, and a pacing pulse from the first electrode deloads the vulnerable region during systole compared to the intrinsic heartbeat. The second electrode is positioned near a ventricular region that is located far from the fragile region, and the pacing pulse from the second electrode is during systole compared to the intrinsic heartbeat It is designed to load vulnerable areas. The device operates in a fragile zone deload mode that delivers pacing pulses into a pacing channel with a first electrode, and intermittently in a fragile zone load mode that delivers pacing pulses into a pacing channel with a second electrode. It should be configured to work.

  The apparatus also includes one or more sensors that sense a variable that can be correlated to the occurrence of myocardial ischemia and is programmed to sense the presence or absence of myocardial ischemia according to the sensed variable. The In various embodiments, the sensor records an electrogram, a heart sensing channel that measures heart rate, an accelerometer that measures activity level or local heart motion, impedance sensitive to local changes in tissue impedance that occurs during ischemia. It may be a sensor and / or a minute ventilation sensor. In this case, the device is configured to switch intermittently to the vulnerable region load mode according to a prescribed schedule, but only to switch to the vulnerable region load mode when the sensed variable indicates myocardial ischemia. For example, the device can sense the patient's effort level (eg, reflecting heart rate, activity level and / or ventilation per minute) and switches intermittently to the vulnerable area load mode, It is preferable that the variable area load mode is intermittently switched only when the variable exists within the specified range.

  The device may also be configured to operate in normal mode when not operating in vulnerable area deload mode or vulnerable area load mode, which may or may not deliver pacing therapy. There is. In one embodiment, for example, the device comprises a third electrode adapted to be placed near a ventricular region remote from the placement location of the first and second electrodes, and the controller sends a pacing pulse to the third Programmed to operate in a normal mode for delivery into a pacing channel with a number of electrodes. In this case, the controller switches to the fragile region deloading mode whenever the sensed variable indicates the presence of myocardial ischemia, and the sensed variable indicates the absence of myocardial ischemia. In some cases, it is programmed to operate intermittently in the vulnerable area load mode or the normal mode at any time. The device may also be configured to switch from the normal mode to the vulnerable area deloading mode if the sensed variable indicates the presence of myocardial ischemia. FIG. 4 illustrates an exemplary algorithm executed by the controller to switch between the normal mode and the vulnerable area reduction or vulnerable area load mode. In step A1, the device operates in a normal mode, which entails delivering some pacing therapy (eg, bradycardia or resynchronized pacing) or no pacing at all. There is a case. In step A2, the device checks whether ischemia is present. If myocardial ischemia is detected, the device operates in the vulnerable area deload mode at step A3 as long as ischemia exists. If myocardial ischemia does not exist, in step A4, the device checks whether it is time to switch to the fragile region loading mode. If so, in step A5, the device determines whether the measured effort level is below a specified value indicating that the patient is at rest. If the patient is in a resting state, the device operates in the vulnerable area load mode in step A6 and remains in that mode until the specified duration determined in step A7 has elapsed.

  In order to provide atrioventricular synchrony, the device is configured to deliver pacing pulses in fragile zone deloading and / or fragile zone loading mode according to atrial tracking or an AV sequential pacing mode with a specified AV delay interval. Is good. To facilitate early excitability in either reduced or loaded mode, the AV delay interval is shorter than the measured intrinsic AV interval so that ventricular intrinsic excitement does not interfere with excitement from early excitatory pacing. Should be set. For example, the AV delay interval may be set to be 50 to 80% of the measured intrinsic AV interval. In one embodiment, the device is configured to measure the patient's intrinsic AV interval and automatically set the AV delay interval according to the measurement.

  The device is also configured to dynamically adjust the AV delay interval to compensate for changes in the patient's inherent AV interval and / or to adjust the amount of early excitement delivered in the vulnerable area deloading and / or load mode. It is good to be. In this embodiment, the device is configured to adjust the AV delay interval according to a sensed variable reflecting myocardial ischemia and / or patient effort level, eg, heart rate, activity level and / or minute ventilation. Is good. FIG. 5 illustrates an exemplary algorithm that can be executed by the controller while delivering early excitement pacing in a weak region deload or load mode. In step B1, the device delivers early excitement pacing at the designated AV delay interval. In step B2, the device obtains a measurement of the patient's effort level, which may be an instantaneous measurement or an average measurement. In step B3, the AV delay interval is computed as a function of an executable work level measurement, for example as a look-up table. Under normal circumstances, the AV delay interval decreases as the measurement effort level increases and vice versa. In step B4, the AV delay interval is set to a computer-calculated value, and the process returns to step B1 to continue early excitation pacing with a new AV delay interval.

  In another embodiment, the patient comprises means for switching the device to the fragile region loading mode, to the fragile region deloading mode and / or to the normal mode when presenting symptoms of myocardial ischemia. Such means may be, for example, a patient operated switch interfaced to the device controller, such as a magnetically activated or contact activated switch. The patient may further comprise means for communicating to the device by telemetry, for example from a remote monitor, in order to issue a command to switch to the selected mode.

  The invention has been described in connection with the specific embodiments described above. It should be understood that these embodiments can be combined with each other in any manner deemed advantageous. Many substitutions, modifications and alterations will also be apparent to those skilled in the art. Such other substitutions, modifications, and alterations are within the scope of the present invention as set forth in the appended claims.

Claims (10)

A device for the heart,
An implantable housing that houses the electronic circuit;
A sensor that senses a variable that can be correlated to the occurrence of myocardial ischemia in the patient;
A first electrode adapted to be placed near a ventricular region that is vulnerable to ischemia;
A second electrode adapted to be disposed near a ventricular region far from the fragile region;
A pulse generator for outputting pacing pulses;
A controller programmed to deliver pacing pulses into the pacing channel in accordance with a programmed pacing mode;
The controller is programmed to detect the presence or absence of myocardial ischemia according to the sensed variable;
The controller operates in a fragile zone deloading mode that sends pacing pulses into a pacing channel with the first electrode or a fragile zone loading mode that sends pacing pulses into a pacing channel with the second electrode. Programmed,
The controller operates in the fragile region deload mode when the sensed variable indicates the presence of myocardial ischemia and the sensed variable indicates the absence of myocardial ischemia An apparatus programmed to operate in the vulnerable area load mode.   The sensor is a cardiac sensing channel that senses cardiac electrical activity, the sensed variable is an electrogram, and the controller detects myocardial ischemia if a damaging current is found in the electrogram. The apparatus of claim 1 programmed to detect the presence of.   The apparatus of claim 1, wherein the sensor is a cardiac sensing channel that senses cardiac electrical activity, and the sensed variable is a heart rate.   The apparatus of claim 1, wherein the sensor is an accelerometer that measures a patient's activity level.   The apparatus of claim 1, wherein the sensor is a minute ventilation sensor. The controller is
Whenever the sensed variable indicates the presence of myocardial ischemia, it switches to the vulnerable area deloading mode,
6. Apparatus according to any one of the preceding claims, programmed to switch to the vulnerable area loading mode whenever the sensed variable indicates the absence of myocardial ischemia.   6. The controller of any one of claims 1-5, wherein the controller is programmed to intermittently switch to the vulnerable area load mode if the sensed variable indicates the absence of myocardial ischemia. The device described in 1. A third electrode adapted to be disposed in the vicinity of a ventricular region remote from the location of the first electrode and the second electrode;
The controller is programmed to operate in a normal mode that sends pacing pulses into a pacing channel with the third electrode;
The controller is
Whenever the sensed variable indicates the presence of myocardial ischemia, it switches to the vulnerable area deloading mode,
2. Programmed to operate intermittently in either the vulnerable area loading mode or the normal mode whenever the sensed variable indicates the absence of myocardial ischemia. The device according to any one of 5.   The controller is programmed to operate in the vulnerable area load mode according to a prescribed schedule, wherein the sensed variable indicates the absence of myocardial ischemia. 6. A device according to any one of claims 1 to 5, which is only allowed in cases.   10. The switch of any of claims 1-9, further comprising a patient actuated switch, wherein the controller is programmed to switch to the fragile zone deload mode when the patient actuated switch is actuated. A device according to claim 1.

Images